Haemophilus influenzae (Hi) is a class of non-motile, spore-free, rod-shaped Gram-negative bacilli that live in the respiratory tract of normal people and are opportunistic pathogens, mainly causing upper respiratory infections, otitis media and pneumonia, as well as sepsis, meningitis and other serious infections in children.
Haemophilus influenzae can be divided into capsular (typeable) and non-capsular (nontypeable). The capsular Haemophilus influenzae can be classified into 6 serotypes, a, b, c, d, e and f according to the components of the capsular polysaccharide. The non-capsular is also called nontypeable Haemophilus influenzae (NTHI).
Haemophilus influenzae invasive diseases occur all over the world. Haemophilus influenzae serotype B (Hib) is the most toxic and the main pathogenic bacterium which can cause bacterial meningitis in children under 5 years of age. The incidence of Haemophilus influenzae serotype b has been declined significantly with the worldwide promotion and use of the Hib conjugate vaccine, which is developed based on Haemophilus influenzae serotype b capsular polysaccharide. The capsular polysaccharide is the major antigenic substance of Haemophilus influenzae and may induce a protective immune response in the human body, however, the capsular polysaccharide is a thymus-independent antigen, which can only produce weak IgM antibodies but does not lead to immune memory, and cannot effectively protect infants and children within 2 years of age. Vaccine developers conjugate the capsular polysaccharide to a protein carrier to form a polysaccharide-protein conjugate vaccine, wherein the protein carrier changes the polysaccharide antigen from the thymus-independent antigen to the thymus-dependent antigen, thereby activating T helper lymphocytes and prompting B cells to produce specific IgG antibodies The Hib conjugate vaccine is now widely used in the world. However, the Hib conjugate vaccine is effective only against Haemophilus influenzae serotype b, and cannot prevent infections by other serotypes of Haemophilus influenzae and nontypeable Haemophilus influenzae, resulting in a substantial increase in the infection rates of other serotypes of Haemophilus influenzae and nontypeable Haemophilus influenzae. For example, the nontypeable Haemophilus influenzae may cause otitis media (OM), the Egyptian biota of Haemophilus influenzae may cause epidemic conjunctivitis and Brazilian purpuric fever. Vaccines for the prevention of Haemophilus influenzae other than serotype b or nontypeable Haemophilus influenzae have not yet been approved so far in the world.
The D protein (HiD) is a lipoprotein on the surface of Haemophilus influenzae and has a relative molecular weight of 42 KDa. The D protein is highly conserved in all Haemophilus influenzae strains (including Haemophilus influenzae with and without capsule), and is a specific antigen of human immunoglobulin D. Although the D protein is effective in preventing otitis media caused by NTHi, HiD has a relatively low molecular weight and a weak immunogenicity.
Hin47 (also known as HtrA) is a heat shock protein expressed by Haemophilus influenzae under ambient pressure, which has serine protease activity. Hin47 is an important immune antigen, which can stimulate the body to produce B cells and T cell responses as evidenced by experiments, and thus its immunogenicity has been fully confirmed.